Tuberous sclerosis complex (TSC): neurocutaneous syndrome

Clinical History

A 14-year-old female patient presented with epilepsy, mental retardation and mucocutaneous lesions.

Imaging Findings

A 14-year-old female patient presented for CT brain with history of recurrent episodes of epilepsy since childhood. On clinical history, she was having below average mental and cognitive abilities. Hence she had left schooling in the early childhood as she was not able to cope with the studies.

On examination, she had a dull look, expressionless facial features without any social smile with depressive look. She had multiple, discrete, reddish papular lesions over the cheeks, nose and forehead suggestive of adenoma sebaceum. A pinkish nevus was also seen at the lower eyelid of left eye near the outer canthus [Fig. 1a,b].

NCCT and CECT brain was performed and showed multiple calcified lesions in the cortical, subcortical and subependymal region, especially along the lateral ventricles and at foramen of monro [Fig. 2a,b].Few iso to slightly hyperdense lesions were also noted, which showed minimal enhancement on contrast administration. The cortical and subcortical hamartomatous tuberous lesions were oval to pyramidal in shape and few of these calcified lesions showed their tip facing towards the bodies of lateral ventricles [Fig. 3]. No evidence of heterotopia was noted. No features of obstructive hydrocephalus were noted.

Abdominal Sonography was done and which showed multiple bilateral simple cysts [Fig. 4] with a heterogenously echogenic area suggestive of angiomyolipoma in the lower pole of the left kidney [Fig. 5].

Keeping in view the triad of adenoma sabaceum, epilepsy and mental retardation, the diagnosis of mucocutaneous syndrome of tuberous sclerosis complex was made.

Discussion

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease primarily affecting the skin and central nervous system. It results from mutation of two different genes hamartin (TSCI) & tuberin (TSCII) located at chromosomes 9 & 16 [1].These genes act as tumour suppressors, their mutation leads to hamartomatous lesions in various organs including the skin. The ‘classical triad’ consists of adenoma sebaceum, epilepsy and mental retardation. TCS is also known as Bournervlle’s disease as described by Bournevlle, a French physician in 1880 [2,3].

Tuberous sclerosis complex has a wide range of mucocutaneous manifestations that includes adenoma sebaceum (angiofibroma), connective tissue nevi (shagreen’s patches), hypomelanotic macules (Ash leaf macules), periungual fibromatous lesions (koenen’s tumours), fibromatous plaque on forehead, and oral mucosal fibromas. Adenoma sebaceum is the commonest cutaneous manifestation characterised by multiple, discrete, translucent, reddish papules that are distributed symmetrically around the nose, cheeks and forehead. The incidence of tuberous sclerosis complex is estimated at 1/10,000 [3].

Radiological features of Tuberous sclerosis complex are:

Cerebral: Intracranial pathology can be complex involving cortical, subcortical, subependymal and cerebellar tissues. Hamartomatous lesions or tubers are seen in the brain which are tuberosclerotic nodules of glial proliferation. The number of tubers in the cortex and subcortex appears to correlate with the clinical severity of the disease, as measured by the ease of control of seizures, developmental milestones, and school performance.

Plain X ray film findings may show discrete or gyriform calcifications.

CT scan shows hamartomatous tubers at various stages of development. Cortical and subcortical hamartomatous lesions may appear iso to slightly hyperdense on non-contrast CT scan, better delineated on contrast enhanced scans. The cortical tuber may vary in shape and triangular lesions points towards the lateral ventricular system. 90% of tubers may show calcifications, especially in periventricular and subependymal regions. Calcified tubers are commonly seen at foramen of monro, few of them may transform into giant cell astrocytomas causing obstructive changes [4,5].

MRI is superior for identifying parenchymal tubers, which appears as low or intermediate signal on T1W, high signal on T2W and variable intensity on proton density weighted images. Subependymal hamartomas have similar intensity to white matter showing enhancement in 30% cases. Periventricular nodular heterotopia may present with epilepsy and mental retardation [4].

Renal involvement occurs in 60% cases of TSC and commonest lesion being an angiomyolipoma. When multiple and bilateral, they are pathognomonic of TS. Sonography shows heterogeneous masses, primarily echogenic owing to fat contents. Multiple cysts occur in combination with AML in 20% of cases.

Skeletal manifestations: sclerosis, patchy and dense due to thickening of calvarium and periosteal thickening of long bones. The subungual fibromas cause pressure erosion of terminal phalanges leading to acro-osteolysis [5,6].

Cardiac rhabdomyomas occur exclusively in TSC and present in neonatal period. They can be detected on echocardiography as smooth, ovoid, hyperechoic lesions [4].

The treatment in cases of TSC is mostly symptomatic with antiepileptics and treatment of skin lesions. Surgery is advised if tuber is single [6]. Sirolimus therapy is advised in angiomyolipomas [7].

Differential Diagnosis List

Final Diagnosis

Tuberous sclerosis complex

URL:	https://www.eurorad.org/case/8755
DOI:	10.1594/EURORAD/CASE.8755
ISSN:	1563-4086